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Merck's LAG-3 plus Keytruda combo fails Phase 3 in colorectal cancer

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Merck’s efforts to combine its PD-1 blockbuster Keytruda with an experimental LAG-3 inhibitor hit a stumbling block Wednesday morning.

The company said a Phase 3 study testing the LAG-3 program favezelimab in combination with Keytruda did not improve overall survival figures when compared to standard of care, failing its primary endpoint. Researchers were evaluating the combo in a metastatic colorectal cancer setting where patients had previously been treated with a PD-L1 therapy and the DNA in their cells were considered “microsatellite stable.”

It’s a blow for Merck, which is trying to catch Bristol Myers Squibb in developing an approved dual PD-1/LAG-3 combination therapy. But this setting has proved tricky. Bristol Myers’ treatment, called Opdualag that combines Opdivo with relatlimab, also failed a Phase 3 study in microsatellite stable metastatic colorectal cancer late last year.

In addition to colorectal cancer, Merck is attempting to develop the combination in bladder cancer, melanoma, hematological malignancies and esophageal cancer, among others.


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